Early activation marker expression to detect impaired proliferative responses to pokeweed mitogen and tetanus toxoid: studies in patients with AIDS and related disorders.

Abstract

We tested the premise that measurement of interleukin 2 receptor (IL2R) and transferrin receptor (TR) can be used to assess proliferative responses to pokeweed mitogen (PWM) and tetanus toxoid (TT). Our study group consisted of patients with Human Immunodeficiency Virus (HIV) infection, including patients with acquired immunodeficiency syndrome (AIDS, n = 10), AIDS-related complex (n = 14), lymphadenopathy syndrome (n = 7), or homosexual men seropositive for HIV (n = 6). Controls were 40 healthy seronegative blood donors. IL2R and TR expression by stimulated mononuclear cells were assessed using specific monoclonal antibodies and flow cytometry, and results were analyzed using the 3H-thymidine assay for DNA synthesis as a standard for comparisons. For identifying low PWM responses, both the IL2R+ cell percent and the IL2R+ cell number (no.) per lymphocyte trigger region (a relative measure of IL2R+ cell no. per culture) on day 3 (72 h) were sensitive (greater than 90%) and specific (80%); day 3 TR+ cell no. was also sensitive (92%) and specific (100%). For detecting low TT-induced responses, day 7 IL2R+ cell no. proved the most sensitive (100%) and specific (78%) parameter. These findings indicate that cytofluorometric analysis of IL2R and/or TR expression is a reliable method for detecting impaired proliferative responses to PWM and TT in these patients. Such a method offers an attractive alternative to the regulatory and disposal problems associated with radioactivity in the conventional DNA synthesis assay, as well as providing insight to the mechanism(s) responsible for impaired proliferation.